{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:13:47Z","timestamp":1789913627376,"version":"4.0.1"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Leishmaniasis, caused by infection with the protozoan parasite<jats:italic>Leishmania<\/jats:italic>, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen<jats:italic>Leishmania<\/jats:italic>homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with<jats:italic>Leishmania braziliensis<\/jats:italic>. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-\u03b3) production by several different sources, listed in order of contribution: CD4<jats:sup>+<\/jats:sup>T lymphocytes, CD4<jats:sup>\u2212<\/jats:sup>, CD8<jats:sup>\u2212<\/jats:sup>lymphocytes, and CD8<jats:sup>+<\/jats:sup>T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-\u03b3 and tumor necrosis factor alpha (TNF-\u03b1) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4<jats:sup>+<\/jats:sup>T lymphocytes (IFN-\u03b3<jats:sup>+<\/jats:sup>and IL-10<jats:sup>\u2212<\/jats:sup>\/IL-4<jats:sup>\u2212<\/jats:sup>), Tc1 CD8<jats:sup>+<\/jats:sup>T cells (IFN-\u03b3<jats:sup>+<\/jats:sup>, and IL-10<jats:sup>\u2212<\/jats:sup>\/IL-4<jats:sup>\u2212<\/jats:sup>), and a high frequency of TNF-\u03b1-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.<\/jats:p>","DOI":"10.1128\/iai.69.5.3232-3239.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:18Z","timestamp":1027763898000},"page":"3232-3239","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis"],"prefix":"10.1128","volume":"69","author":[{"given":"R. L. A.","family":"Bottrel","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Biochemistry-Immunology,1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. O.","family":"Dutra","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Morphology,2 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. A.","family":"Martins","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Biochemistry-Immunology,1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Gontijo","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->UFMG Medical Center,3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Belo Horizonte, Minas Gerais, UFBA Medical Center,4 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Barral-Netto","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Belo Horizonte, Minas Gerais, UFBA Medical Center,4 and"},{"name":"<!--label omitted: 5-->CPqGM-FIOCRUZ,5 Salvador, Bahia, Brazil, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Barral","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Belo Horizonte, Minas Gerais, UFBA Medical Center,4 and"},{"name":"<!--label omitted: 5-->CPqGM-FIOCRUZ,5 Salvador, Bahia, Brazil, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. P.","family":"Almeida","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Belo Horizonte, Minas Gerais, UFBA Medical Center,4 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Mayrink","sequence":"additional","affiliation":[{"name":"<!--label omitted: 6-->Department of Parasitology,6 Universidade Federal de Minas Gerais (UFMG) and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Locksley","sequence":"additional","affiliation":[{"name":"<!--label omitted: 7-->UCSF Medical Center, San Francisco, California7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. J.","family":"Gollob","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Biochemistry-Immunology,1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.4049\/jimmunol.152.12.5949","article-title":"Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis","volume":"152","author":"Carvalho E. M.","year":"1994","unstructured":"Carvalho E. M. Bacellar O. Brownell C. Regis T. Coffman R. L. Reed S. G. Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis.J. Immunol.152199459495956","journal-title":"J. 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